The concept of molecular structure is traditionally considered to be virtually fundamental. However, it breaks down in extremely flexible molecules, whose dynamics are governed by large-amplitude motions. For the dynamics of molecules with free internal rotations, we therefore propose a five-dimensional rigid rotor model, with states characterized by two generalized angular momentum quantum numbers and a rotational constant B. The quantum numbers characterize a 5D angular-momentum vector, super-j, which describes collective rotations that involve both the internal and the overall rotation...

A system-wide understanding of cellular function requires knowledge of all functional interactions between the expressed proteins. The STRING database aims to collect and integrate this information, by consolidating known and predicted protein-protein association data for a large number of organisms. The associations in STRING include direct (physical) interactions, as well as indirect (functional) interactions, as long as both are specific and biologically meaningful. Apart from collecting and reassessing available experimental data on protein-protein interactions, and importing known pathways and protein complexes from curated databases, interaction predictions are derived from the following sources: (i) systematic co-expression analysis, (ii) detection of shared selective signals across genomes, (iii) automated text-mining of the scientific literature and (iv) computational transfer of interaction knowledge between organisms based on gene orthology...

BACKGROUND: Several studies have shown that mammographic texture features are associated with breast cancer risk independent of the contribution of breast density. Thus, texture features may provide novel information for risk stratification. We examined the association of a set of established texture features with breast cancer risk by tumor type and estrogen receptor (ER) status, accounting for breast density. METHODS: This study combines five case-control studies including 1171 breast cancer cases and 1659 controls matched for age, date of mammogram, and study...

Importance: Shift-to-shift transitions in care among house staff are associated with adverse events. However, the association between end-of-rotation transition (in which care of the patient is transferred) and adverse events is uncertain. Objective: To examine the association of end-of-rotation house staff transitions with mortality among hospitalized patients. Design, Setting, and Participants: Retrospective multicenter cohort study of patients admitted to internal medicine services (N = 230 701) at 10 university-affiliated US Veterans Health Administration hospitals (2008-2014)...

OBJECTIVE: Therapeutic drug monitoring (TDM) of clozapine is standardized to 12-h postdose samplings. In clinical settings, sampling time often deviates from this time point, although the importance of the deviation is unknown. To this end, serum concentrations (s-) of clozapine and its metabolite N-desmethyl-clozapine (norclozapine) were measured at 12 ± 1 and 2 h postdose. METHOD: Forty-six patients with a diagnosis of schizophrenia, and on stable clozapine treatment, were enrolled for hourly, venous blood sampling at 10-14 h postdose...

Slope failure like in the Hinlopen/Yermak Megaslide is one of the major geohazards in a changing Arctic environment. We analysed hydroacoustic and 2D high-resolution seismic data from the apparently intact continental slope immediately north of the Hinlopen/Yermak Megaslide for signs of past and future instabilities. Our new bathymetry and seismic data show clear evidence for incipient slope instability. Minor slide deposits and an internally-deformed sedimentary layer near the base of the gas hydrate stability zone imply an incomplete failure event, most probably about 30000 years ago, contemporaneous to or shortly after the Hinlopen/Yermak Megaslide...

OBJECTIVES: The AspireAssist System (AspireAssist) is an endoscopic weight loss device that is comprised of an endoscopically placed percutaneous gastrostomy tube and an external device to facilitate drainage of about 30% of the calories consumed in a meal, in conjunction with lifestyle (diet and exercise) counseling. METHODS: In this 52-week clinical trial, 207 participants with a body-mass index (BMI) of 35.0-55.0 kg/m(2) were randomly assigned in a 2:1 ratio to treatment with AspireAssist plus Lifestyle Counseling (n=137; mean BMI was 42...

PURPOSE: To validate the diagnostic codes for Charcot-Marie-Tooth disease (CMT) in the Danish National Patient Registry (DNPR) using positive predictive value (PPV) as a measure of validity. PATIENTS AND METHODS: We used the DNPR to identify all patients diagnosed with at least one primary CMT diagnosis at a specialized department in the Central Denmark Region during the period 1977-2012. From this population, we randomly selected 123 patients for the validation study...

: CarD is an essential RNA polymerase (RNAP) interacting protein in Mycobacterium tuberculosis (Mtb) that stimulates formation of RNAP-promoter open complexes. CarD plays a complex role in Mtb growth and virulence that is not fully understood. Therefore, to gain further insight into the role of CarD in Mtb growth and virulence we determined the effect of increasing the affinity of CarD for RNAP. Using site-directed mutagenesis guided by crystal structures of CarD bound to RNAP, we identified amino acid substitutions that increase the affinity of CarD for RNAP...

Genome-wide association studies have identified >50 common variants associated with kidney function, but these variants do not fully explain the variation in eGFR. We performed a two-stage meta-analysis of associations between genotypes from the Illumina exome array and eGFR on the basis of serum creatinine (eGFRcrea) among participants of European ancestry from the CKDGen Consortium (nStage1: 111,666; nStage2: 48,343). In single-variant analyses, we identified single nucleotide polymorphisms at seven new loci associated with eGFRcrea (PPM1J, EDEM3, ACP1, SPEG, EYA4, CYP1A1, and ATXN2L; PStage1<3...

: Habituation (i.e., decreases in responding) and sensitization (i.e., increases in responding) following prolonged or repeated exposures to a fixed stimulus, have been identified as important in adaptation to repeated or prolonged noxious stimulation. Determinants of habituation or sensitization are poorly understood, and experimental investigation of habituation of pain ratings have generally relied on pain reports and statistical techniques that average responses across a group of participants...

BACKGROUND: The aim of this study was to examine the influence of ezetimibe in addition to atorvastatin on plaque composition in patients with first-time ST-segment Elevation Myocardial Infarction treated with primary percutaneous intervention. METHODS: Eighty-seven patients were randomized (1:1) to ezetimibe 10mg or placebo in addition to Atorvastatin 80mg. Intravascular ultrasound with iMap was performed at baseline and after 12months in a non-infarct-related artery...

BACKGROUND: Natalizumab reduces disease activity in multiple sclerosis (MS). Natalizumab binds to the very late antigen-4 and inhibits vascular cell adhesion molecule-1 (VCAM-1)-mediated transmigration of immune cells across the blood-brain-barrier. This is associated with decreased serum concentrations of soluble (s)VCAM-1 and an altered composition of immune cell-subsets in the blood. OBJECTIVE: We aimed to examine if sVCAM-1 serum concentrations and whole blood mRNA expression levels of immune activation biomarkers is associated with disease activity in natalizumab-treated MS-patients...

DESIGN: This study was conducted as a randomized, double blind, placebo-controlled parallel group trial preceded by open label enrichment phase. OBJECTIVES: The objectives of this study were 1) to examine the effect of SR-Fampridine treatment on muscle strength in terms of maximal voluntary contraction (MVC) and rate of force development (RFD) of the lower extremities and 2) to replicate previously published data on the effect of slow release-Fampridine (SR-Fampridine) on the functional capacity of the lower limbs, the upper limb and cognitive function, in persons with multiple sclerosis (pwMS)...

This article provides an overview of studies addressing effects of ionizing radiation on the heart. Clinical studies have identified early and late manifestations of radiation-induced heart disease, a side effect of radiation therapy to tumors in the chest when all or part of the heart is situated in the radiation field. Studies in preclinical animal models have contributed to our understanding of the mechanisms by which radiation may injure the heart. More recent observations in human subjects suggest that ionizing radiation may have cardiovascular effects at lower doses than was previously thought...

OBJECTIVE To determine the source of a healthcare-associated outbreak of Pantoea agglomerans bloodstream infections. DESIGN Epidemiologic investigation of the outbreak. SETTING Oncology clinic (clinic A). METHODS Cases were defined as Pantoea isolation from blood or catheter tip cultures of clinic A patients during July 2012-May 2013. Clinic A medical charts and laboratory records were reviewed; infection prevention practices and the facility's water system were evaluated. Environmental samples were collected for culture...

Maternally inherited mitochondrial (mt)DNA mutations can cause fatal or severely debilitating syndromes in children, with disease severity dependent on the specific gene mutation and the ratio of mutant to wild-type mtDNA (heteroplasmy) in each cell and tissue. Pathogenic mtDNA mutations are relatively common, with an estimated 778 affected children born each year in the United States. Mitochondrial replacement therapies or techniques (MRT) circumventing mother-to-child mtDNA disease transmission involve replacement of oocyte maternal mtDNA...

Social protection programmes are designed to help vulnerable populations - including pastoralists - maintain a basic level of well-being, manage risk, and cope with negative shocks. Theory suggests that differential targeting according to poverty status can increase the reach and effectiveness of budgeted social protection programmes. Chronically poor households benefit most from social protection designed to help them meet their basic needs and make vital investments necessary to graduate from poverty. Vulnerable non-destitute households benefit from protection against costly temporary shocks, but do not necessarily need regular assistance...